title: Hydrogen peroxide modulates phenylephrine-induced contractile response in renal hypertensive rat aorta.
abstract: Endothelium-derived factors play an important role in vascular tone control. This study aimed to evaluate how endothelium and reactive oxygen species (ROS) contribute to phenylephrine (PE)-induced contraction in renovascular hypertensive (2K-1C) and normotensive (2K) rats aortas. The effects of the superoxide scavenger Tiron (0.1mM and 1mM) or catalase (30 U/ml, 90 U/ml, 150 U/ml and 300 U/ml) on the PE-induced contraction were evaluated in both intact endothelium (E+) and denuded (E-) aortas. Endothelium removal increased the PE-induced contractions. The maximum contractile response decreased only in 2K-1C rat E+ aorta, and catalase (30 U/ml, 90 U/ml, 150 U/ml) partially reversed this effect. Endothelium increased the basal hydrogen peroxide (H2O2) production in 2K and 2K-1C rats aortas. PE-stimulated H2O2 production was higher in 2K-1C (E+/E-) than in 2K (E+/E-). Inhibition of the enzymes cyclooxygenase, NADPH-oxidase, xanthine-oxidase, and superoxide dismutase reduced the PE-stimulated H2O2 production in 2K-1C rat aorta. The decreased contraction to PE in 2K-1C rat aorta is partially due to endothelial H2O2 production; however, in denuded aorta, it contributes to maintaining the contractile response. Superoxide plays an important role on the PE-induced contraction in 2K rat denuded aorta, whereas in 2K-1C rat aorta, it is H2O2 that plays an important role in this effect.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Bruno R
authors.initials: BR
authors.lastname: Silva
authors.forename: Laena
authors.initials: L
authors.lastname: Pernomian
authors.forename: Marcella D
authors.initials: MD
authors.lastname: Grando
authors.forename: Jefferson H
authors.initials: JH
authors.lastname: Amaral
authors.forename: José E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology*; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018340:Receptors, Adrenergic, alpha-1; C070295:catalase-polyethylene glycol; D013481:Superoxides; D010656:Phenylephrine; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: 2K–1C renal hypertension; Adrenergic α(1) agonist; Contractile response; Endothelial factor; Oxygen radical